Protective effect of Sox11 gene against cerebral ischemia reperfusion injury and its mechanism in mice / 中国生物制品学杂志

@#ObjectiveTo explore the protective effect of Sox11 gene on cerebral ischemia reperfusion injury(CIRI)in mice and its mechanism,so as to provide a new target for the treatment of CIRI.MethodsThe mouse middle cerebral artery occlusion(MCAO)model and Neuro2A cell oxygen glucose deprivation reperfusion(OGDR)model were established and detected for the temporal and spatial distribution of Sox11 in the models by real-time quantitative PCR,Western blot,immunohistochemistry(IHC)and immunohistofluorescence(IHF).The altered expression of some crucial genes in the pathway of apoptosis and inflammation in OGDR model after the disruption of Sox11 expression was detected by Western blot.ResultsThe expression level of Sox11 mRNA and protein increased significantly in both MCAO and Neuro2A OGDR models(P = 0.000 1 ～ 0.038 8);After CIRI,Sox11 expression was elevated in the hippocampal dentate gyrus(DG)region of mice;After interfering with the expression of Sox11 in OGDR model,the expression of apoptosis-related protein Cleaved Caspase 3 significantly increased,while the expression of anti-apoptosis protein Bcl-2 significantly decreased,and the expression of phosphorylated NF-κB(p-NF-κB)protein related to inflammatory reaction also up-regulated significantly.Conclusion Sox11gene had a protective effect against CIRI in mice,and was involved in the regulation of apoptosis and inflammation pathways after CIRI.

lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11

The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.

Relationship between methylation of SOX11 gene and cervical cancer / 西安交通大学学报(医学版)

Objective: To detect the methylation status of SOX11 gene in normal cervix, cervical cancer tissues and cervical cancer cell lines so as to explore the relationship between methylation status and expression of SOX11 gene. Methods: DNA methylation status of SOX11 gene in normal cervical, cervical cancer tissues and cervical cancer cell lines was analyzed by bisulfite sequencing and TA cloning assay. The expression of SOX11 mRNA in cervical cancer tissues, cell lines and normal cervical was detected by RT-PCR. Results: The average methylation rate of SOX11 in cervical cancer tissues (81.07%) was significantly higher than that in normal cervical tissues (12.86%) (P<0.001). The methylation status of SOX11 in HeLa, SiHa, C33-A and CaSki cells was all hypermethylated with the methylation of 90.71%, 97.14%, 77.14% and 99.64%, respectively. The expression of SOX11 mRNA in cervical cancer tissues was significantly lower than that in normal cervixes (P<0.001). The SOX11 gene expression was significantly negatively correlated with its promoter hypermethylation (P<0.001, r=-0.808). After demethylation agent 5-azacytidine treatment, SOX11 mRNA expression in cervical cancer cell lines was significantly increased. Further analysis showed that HPV infection in cervical cancer might increase SOX11 promotor methylation. Conclusion: SOX11 gene in cervical cancer is silenced by the hypermethylation of DNA in the promoter region.

Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma / 中华血液学杂志

Objective@#To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism.@*Methods@#Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay.@*Results@#①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3′ untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001).@*Conclusions@#The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.

Progress of differential expression of SOX11 in mantle cell lymphoma / 白血病·淋巴瘤

Overexpression of CCND1 and t (11;14) (q13;q32) chromosomal translocation are important markers in mantle cell lymphoma (MCL). However, part of MCL lacks the expression of CCND1. SOX11 can be used as a biomarker for its overexpression in CCND1-negative MCL. SOX11 is a neurogenic transcription factor, and its overexpression is closely related to histone modification and DNA methylation. Differential expression of SOX11 in MCL is closely related with the plasma cell differentiation, and there is a relationship between the prognosis and survival time of MCL. SOX11 cDNA is more sensitive than conventional methods for the detection of minimal residual disease (MRD). With further research of SOX11, it will become an important basis of diagnosis and prognosis in MCL, and can provide a new method for targeted therapy of MCL.

The expression and clinical significance of Sox 11 in cervical carcinogenesis / 西安交通大学学报(医学版)

Objective To explore the expression level of Sox11 gene in cervical cancer cell lines and cervical pathology tissue .Methods The expression of Sox11 protein was detected in cervical cancer cell lines HeLa , CaSki ,SiHa and C-33A as well as NC ,LSIL ,HSIL and CC using immunohistochemistry and Western blot .We analyzed the relationship between Sox11 expression in cervical cancer and clinicopathologic parameters .Results The expression of Sox11 protein in normal cervical tissue ,low-grade cervical squamous intraepithelial neoplasia was significantly higher than that in the high-grade cervical squamous intraepithelial neoplasia and invasive cervical cancer tissue , and the expression was reduced with the progression of cervical lesions .The expression of Sox11 protein in the invasive cervical cancer was reduced with increased malignant degree .The expression of Sox11 protein in the invasive cervical cancer was significantly correlated with HPV infection ,but not associated with the age , clinical stage ,lymph node metastasis or muscular infiltration depth .Conclusion Sox11 expression is negatively correlated with cervical cancer development ,suggesting that as a tumor suppressor gene ,Sox11 may play a role in cervical cancer development and its absence or low expression is associated with the development of cervical cancer and is an early event of cervical carcinogenesis and may be a sign of malignant change of cervical tissue .

Expresión del factor de transcripción SOX11: Su implicancia en el linfoma de células del manto / Expression of SOX11 transcription factor: Its implication in mantle cell lymphoma

El gen SOX11, perteneciente a la familia de genes SOXC, es un factor de transcripción involucrado en la neurogénesis embrionaria y el remodelado tisular, participando asimismo en el control de la proliferación celular. Su rol en la linfomagénesis es desconocido. Estudios recientes han mostrado expresión proteica nuclear aberrante y sobreexpresión de los niveles de transcripto de SOX11 en pacientes con linfoma de células del manto (LCM). Si bien la mayoría de estos linfomas presentan un curso clínico agresivo, existe un subgrupo de pacientes con enfermedad indolente, sugiriendo una mayor heterogeneidad de esta patología. Actualmente, existen contradicciones respecto de la asociación entre la expresión del gen SOX11 y la evolución clínica del LCM; mientras algunos autores relacionan la ausencia de expresión de SOX11 con buen pronóstico, otros lo encuentran asociado a un curso clínico adverso. Esta diferencia en la expresión estaría relacionada a mecanismos epigenéticos, metilación del ADN y modificaciones a nivel de histonas, que permitirían la expresión aberrante de este gen en algunas neoplasias linfoides, incluyendo LCM. La profundización del conocimiento del gen SOX11 en LCM hará factible, sin duda, lograr una mayor comprensión de los mecanismos involucrados en la patogénesis y/o progresión de este linfoma, así como del rol de SOX11 en estos procesos.

SOX11, belonging to the family of genes SOXC, is a transcript factor involved in the embryonic neurogenesis and tissue remodeling, also participating in the control of cell proliferation. Its role in lymphomagenesis still remains unknown. Recent studies have shown aberrant SOX11 nuclear protein expression as well as mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of these lymphomas have an aggressive clinical course, there is a subgroup of patients with an indolent clinical evolution, suggesting a greater heterogeneity of this disease. Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. This difference in the gene expression could be associated to epigenetic mechanisms such as modifications at the histone level and DNA methylation that would allow the aberrant expression of this gene in some lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead to a greater understanding of those mechanisms involved in the pathogenesis and progression of this lymphoma, also the involvement of SOX11 in these processes.